1. Field of the Invention
This invention relates to method and apparatus (and use of same) for ultrasound imaging of organs and tissue by detection of ultrasound backscatter from a body region containing a contrast agent.
2. Related Art
Ultrasound tissue imaging typically involves projecting an ultrasound acoustic beam from a transceiver transducer probe to a zone of tissue to be imaged, receiving (via such transceiver transducer probe) the acoustic echo reflected from the tissue as an ultrasound response signal (sometimes referred to as a "radiofrequency" response signal), processing the radiofrequency response into a video output signal in suitable signal processing circuits, storing the video output for visual display in a video scan converter, and scanning the entire tissue image region in this manner to produce a video image of the region under investigation on a display device.
Wide acceptance of ultrasound as an inexpensive non-invasive diagnostic technique coupled with rapid development of electronics and related technology has brought about numerous improvements to ultrasound equipment and ultrasound signal processing circuitry. Ultrasound scanners designed for medical or other uses have become cheaper, easier to use, more compact, more sophisticated and more powerful instruments. However, the changes of acoustic impedance occurring within living tissue are small and the absorption of ultrasound energy by different types of tissue (blood vessels, organs, etc.) are such that diagnostic applications do not always follow technical developments.
This situation changed considerably with the development and introduction of administrable ultrasound contrast agents. Introduction of contrast agents made from suspensions of gas microbubbles or microballoons into organs to be investigated have demonstrated that better ultrasound images of organs and surrounding tissue may be obtained with standard ultrasound equipment. Thus, organs like the liver, spleen, kidneys, heart or other soft tissue have become more clearly visible, which opened up new diagnostic areas for both B-mode and Doppler ultrasound and broadened the use of ultrasound as a diagnostic tool.
Unfortunately, so far, ultrasound contrast agents and ultrasound techniques i.e., scanners, electronic circuitry, transducers and other hardware have rarely been studied and developed together. Almost independent developments of these otherwise related segments of the field resulted in incremental improvements of the respective products and systems; however, this has provided no opportunity to draw on synergies offered by studies in which the electronic/ultrasound characteristics of the apparatus and the physical properties of the contrast agent are combined. A few isolated examples of such studies reported improvements for specific agents/equipment combinations, however, the solutions reported are too limited. More universal methods for producing greater tissue resolution, better image and greater versatility of ultrasound as a diagnostic technique would be welcomed and, provided their implementation is kept relatively simple, would be widely accepted.
Thus a large number of documents describe various developments in the field of medical ultrasound apparatus and imaging, as for example U.S. Pat. No. 4,803,993, U.S. Pat. No. 4,803,994, U.S. Pat. No. 4,881,549, U.S. Pat. No. 5,095,909, U.S. Pat. No. 5,097,836, etc. However, although these documents deal with realtime systems and methods, they do not take into consideration physical properties of the contrast agent. In fact they are not concerned with the contrast agent at all.
An attempt towards improved ultrasound imaging using contrast agents is described in WO-A-93/12720 and/or its U.S. counterpart U.S. Pat. No. 5,255,683 (Monaghan) which discloses a method of imaging a region of the body based on subtracting non-displayed ultrasound "images" obtained prior to injection of a contrast agent from the non-displayed "images" of the same region obtained following administration of the contrast agent. Based on this response subtraction principle, the method performs superposition of images obtained from the same region prior to and after administration of the contrast agent, providing an image of the region perfused by the contrast agent freed from background image, noise and artifacts. In theory, the method described is capable of providing good quality images with enhanced contrast.
However, in practice, such image substraction processing techniques require maintenance of the same reference position of the region imaged for a long period of time, i.e., long enough to allow injection and perfusion of the contrast agent and maintenance and processing of an enormous amount of data. Therefore practical implementation of the Monaghan method is very difficult if not impossible. The difficulty is partly due to inevitable internal body movements related to breathing, digestion and heart beat, and partly due to movements of the imaging probe by the ultrasound operator. Most realtime imaging probes are commonly handheld for best perception, feedback and diagnosis.
Although at one point Monaghan suggests forming one or both of the non-displayed "images" to be subtracted by comparing ratios of echo signal components at different frequencies, he never suggests display of such an "image" itself as being useful or advantageous.
Interesting proposals for improved imaging of tissue containing microbubble suspensions as contrast agent have been made by Burns, P., Radiology 185 P (1992) 142 and Schrope, B. et al., Ultrasound in Med. & Biol. 19 (1993) 567. There, it is suggested that second harmonic frequencies generated by non-linear oscillation of microbubbles be used as Doppler imaging parameters. The method proposed is based on the fact that normal tissue does not display non-linear responses the same way as microbubbles, and therefore the use of second harmonics allows for contrast enhancement between tissue with and without contrast agent. Although attractive, the method has its shortcomings, as its application imposes several strict requirements.
Firstly, excitation of the fundamental "bubble-resonance" frequency must be achieved by fairly narrow-band pulses, i.e., relatively long tone bursts of several cycles. While this requirement is compatible with the circuits and conditions required by Doppler processing, it becomes inapplicable in the case of B-mode imaging, where the ultrasound pulses necessarily are of very short duration, typically one-half or one-cycle excitation. In this case, insufficient energy is converted from the fundamental frequency to its "second-harmonic," and thus the B-mode imaging mode can hardly be used for this echo-enhancing method.
Secondly, the generated second harmonic is attenuated, as the ultrasound echo propagates in tissue on its way back to the transducer, at a rate determined by its frequency, i.e., at a rate significantly higher than the attenuation rate of the fundamental frequency. This constraint is a drawback of the "harmonic-imaging" method, which is thus limited to propagation depths compatible with ultrasound attenuation at the high "second-harmonic" frequency.
Furthermore, in order to generate echo-signal components at twice the fundamental frequency, "harmonic imaging" requires non-linear oscillation of the contrast agent. Such behavior requires the ultrasound excitation level to exceed a certain acoustic threshold at the point of imaging (i.e. at a certain depth in tissue). During non-linear oscillation, a frequency conversion takes place, causing part of the acoustic energy to be converted from the fundamental excitation frequency up to its second harmonic. On the other hand, that level should not exceed the microbubble burst level at which the micro-bubbles are destroyed, and hence harmonic imaging will fail due to the destruction of contrast agent in the imaging volume.
The above constraints to second harmonic imaging methods thus require that the imaging-instrument is set-up in such a way as to ensure the transmit-acoustic level to fall within a certain energy band: high enough to generate second harmonic components, but low enough to avoid microbubble destruction within a few cycles.
Thus in contrast with these "before" and "after" methods, a method which would treat electronic signals originating from realtime echoes obtained simultaneously and during normal real time ("on the fly") applications would provide a great step is towards better imaging and wider use of ultrasound diagnostic equipment. Such method would be based on an enhancement of echo signals received from regions imaged by signal processing functions which are designed to enhance contrast between regions containing contrast agent from those without contrast agent, on the basis of frequency-response parameters, and would be simple to use and implement in new instrument designs.